Confinement primes cells for faster migration by polarizing active mitochondria

Nanoscale Adv. 2023 Nov 22;6(1):209-220. doi: 10.1039/d3na00478c. eCollection 2023 Dec 19.ABSTRACTMechanical cues in the tumor microenvironment interplay with internal cellular processes to control cancer cell migration. Microscale pores present in tumor tissue confer varying degrees of confinement on migrating cells, increasing matrix contact and inducing cytoskeletal rearrangement. Previously, we observed that increased collagen matrix contact significantly increased cell migration speed and cell-induced strains within the matrix. However, the effects of this confinement on future cell migration are not fully understood. Here, we use a collagen microtrack platform to determine the effect of confinement on priming MDA-MB-231 cancer cells for fast migration. We show that migration through a confined track results in increased speed and accumulation of migratory machinery, including actin and active mitochondria, in the front of migrating breast cancer cells. By designing microtracks that allow cells to first navigate a region of high confinement, then a region of low confinement, we assessed whether migration in high confinement changes future migratory behavior. Indeed, cells maintain their speed attained in high confinement even after exiting to a region of low confinement, indicating that cells maintain memory of previous matrix cues to fuel fast migration. Active mitochondria maintain their location at the front of the cell even after cells leave high confinement. Further...
Source: Adv Data - Category: Epidemiology Authors: Source Type: research